GABAa-receptor binding sitesTBPSPicroloxinineGABA-ReceptorGABAa Ligand-operatedBarbituratesBenzodiazepinesCIChannelNeurosleroldsphosphorylatlon
GABA-Receptor a Ligand-operated Cl- Channel
The chloride channel appears to contain regulatorysites with high affinity for such agents as GABA, thebenzodiazepines,picrotoxin,alcohol, neuroactivesteroids, and the barbiturates.Chloride movement across neuronal membranes canbe regulated at this ion channel by three sites(1) a GABA-binding site(2) a benzodiazepine-binding site(3) a picrotoxin-binding siteGABA and other agonists open the chloridechannel (increase chloride conductance)
The chloride channel appears to contain regulatory sites with high affinity for such agents as GABA, the benzodiazepines, picrotoxin, alcohol, neuroactive steroids, and the barbiturates. Chloride movement across neuronal membranes can be regulated at this ion channel by three sites: (1) a GABA-binding site (2) a benzodiazepine-binding site (3) a picrotoxin-binding site. GABA and other agonists open the chloride channel (increase chloride conductance)
barbituratesBenzodiazepinepicrotoxinalcoholpentylenetetrazol(+) sitemethylxanthiness (+)Other agentsGABA-mediated 个↓chloride ↑1Inhibition of CNS
Benzodiazepine GABA-mediated ↑↓ chloride ↑↓ pentylenetetrazol methylxanthines Other agents barbiturates picrotoxin alcohol Inhibition of CNS
Strychnineappears to be a specific competitive postsynapticantagonist of glycine.Glycine, like GABA, is a known inhibitorytransmitter in the mammalian CNS. Glycinemediates inhibition of spinal cord neurons and isintimately involved in the regulation of spinal cordand brainstem reflexes.Strychnine directly antagonizes thisinhibition, allowing excitatory impulses tobe greatly exaggerated
Strychnine appears to be a specific competitive postsynaptic antagonist of glycine. Glycine, like GABA, is a known inhibitory transmitter in the mammalian CNS. Glycine mediates inhibition of spinal cord neurons and is intimately involved in the regulation of spinal cord and brainstem reflexes. Strychnine directly antagonizes this inhibition, allowing excitatory impulses to be greatly exaggerated
ClinicalUsesAs indicated, most of the analeptic stimulants wereused as pharmacological treatments for overdosage of CNSdepressantsDoxapram (Dopram) is sometimes used to counteractpostanesthetic respiratory depression and as an aid inchronic obstructive pulmonary disease.Pentylenetetrazol (Metrazol) was used experimentally onrare occasions to “activate" the electroencephalogramStrychnine is used almost exclusively in animal studies as atool for studying CNS mechanisms because it is a relativelyspecific glycine antagonist
Clinical Uses As indicated, most of the analeptic stimulants were used as pharmacological treatments for overdosage of CNS depressants. Doxapram (Dopram) is sometimes used to counteract postanesthetic respiratory depression and as an aid in chronic obstructive pulmonary disease. Pentylenetetrazol (Metrazol) was used experimentally on rare occasions to “activate” the electroencephalogram. Strychnine is used almost exclusively in animal studies as a tool for studying CNS mechanisms because it is a relatively specific glycine antagonist